rs722571

Variant names:

• chr19-12700565-T-A
• rs722571
• NM_001382241.1:c.*699A>T

Your query was ambiguous. Multiple possible variants found:

• chr19-12700565-T-A
• chr19-12700565-T-C
• chr19-12700565-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001382241.1(TNPO2):​c.*699A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TNPO2 NM_001382241.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22
• Publications: 17 publications found

Genes affected

TNPO2 (HGNC:19998): (transportin 2) Predicted to enable nuclear import signal receptor activity and nuclear localization sequence binding activity. Predicted to be involved in protein import into nucleus. Predicted to act upstream of or within negative regulation of muscle cell differentiation. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TNPO2 Gene-Disease associations (from GenCC):

• intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TNPO2	NM_001382241.1	c.*699A>T		3_prime_UTR_variant	Exon 26 of 26	ENST00000425528.6	NP_001369170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TNPO2	ENST00000425528.6	c.*699A>T		3_prime_UTR_variant	Exon 26 of 26	5	NM_001382241.1	ENSP00000407182.1
TNPO2	ENST00000356861.9	c.*699A>T		3_prime_UTR_variant	Exon 25 of 25	1		ENSP00000349321.4
TNPO2	ENST00000450764.6	c.*699A>T		3_prime_UTR_variant	Exon 24 of 24	1		ENSP00000397379.2

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 146 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 106

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 118

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 26118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.70
PhyloP100		1.2
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs722571; hg19: chr19-12811379;